In Orientals, ALDH2 deficiency due to a common polymorphism frequently causes a flushing reaction after alcohol consumption and this aversive reaction is responsible for lower rates of alcoholism in individuals with the inactive ALDH2-2 allele. ALDH2 deficiency was detected in South American Indian populations; however, these findings have never been confirmed and a previous search for the Oriental ALDH2-2 allele in South American Indians was negative. Recently R. Peterson has identified a series of additional markers at ALDH2. By restriction enzyme analysis, SSCP and sequencing enabled him to identify haplotypes characteristic for the ALDH2-2 and ALDH2-1 alleles in different populations. This analysis has shed light on the origins and functional role of the variant ALDH2-2 allele, which appears to have appeared on a single haplotype lineage and spread among East Asian populations. Although ALDH22R [Glu487Lys] probably originated on a single genetic background, haplotype analysis reveals that it is sufficiently ancient for additional mutations to have occurred subsequently. The results on ALDH2 haplotypes are most compatible with an effect of selection to maintain the Oriental ALDH2 variant, Glu487Lys.